rs1130698

Variant names:

• chr11-838542-C-A
• rs1130698
• NM_004357.5:c.*350C>A

Your query was ambiguous. Multiple possible variants found:

• chr11-838542-C-A
• chr11-838542-C-G
• chr11-838542-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004357.5(CD151):​c.*350C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000271 in 221,532 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.000027 (0 hom.)
• Consequence: CD151 NM_004357.5 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.959
• Publications: 0 publications found

Genes affected

CD151 (HGNC:1630): (CD151 molecule (Raph blood group)) The protein encoded by this gene is a member of the transmembrane 4 superfamily, also known as the tetraspanin family. Most of these members are cell-surface proteins that are characterized by the presence of four hydrophobic domains. The proteins mediate signal transduction events that play a role in the regulation of cell development, activation, growth and motility. This encoded protein is a cell surface glycoprotein that is known to complex with integrins and other transmembrane 4 superfamily proteins. It is involved in cellular processes including cell adhesion and may regulate integrin trafficking and/or function. This protein enhances cell motility, invasion and metastasis of cancer cells. Multiple alternatively spliced transcript variants that encode the same protein have been described for this gene. [provided by RefSeq, Jul 2008]

POLR2L (HGNC:9199): (RNA polymerase II, I and III subunit L) This gene encodes a subunit of RNA polymerase II, the polymerase responsible for synthesizing messenger RNA in eukaryotes. The product of this gene contains four conserved cysteines characteristic of an atypical zinc-binding domain. Like its counterpart in yeast, this subunit may be shared by the other two DNA-directed RNA polymerases. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004357.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD151	NM_004357.5	MANE Select	c.*350C>A		3_prime_UTR	Exon 9 of 9	NP_004348.2
	CD151	NM_001039490.2		c.*350C>A		3_prime_UTR	Exon 8 of 8	NP_001034579.1
	CD151	NM_139029.2		c.*350C>A		3_prime_UTR	Exon 9 of 9	NP_620598.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CD151	ENST00000397420.9	TSL:1 MANE Select	c.*350C>A		3_prime_UTR	Exon 9 of 9	ENSP00000380565.3
	CD151	ENST00000322008.9	TSL:1	c.*350C>A		3_prime_UTR	Exon 9 of 9	ENSP00000324101.4
	CD151	ENST00000397421.5	TSL:1	c.*350C>A		3_prime_UTR	Exon 8 of 8	ENSP00000380566.1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.0000271 AC: 6 AN: 221532 Hom.: 0 Cov.: 0 AF XY: 0.0000172 AC XY: 2 AN XY: 116572

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.00 AC: 0 AN: 7168

American (AMR) AF: 0.000134 AC: 1 AN: 7450

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 7276

East Asian (EAS) AF: 0.00 AC: 0 AN: 13750

South Asian (SAS) AF: 0.00 AC: 0 AN: 25308

European-Finnish (FIN) AF: 0.000162 AC: 2 AN: 12366

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1002

European-Non Finnish (NFE) AF: 0.0000224 AC: 3 AN: 134204

Other (OTH) AF: 0.00 AC: 0 AN: 13008

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.0
DANN	Benign	0.56
PhyloP100		-0.96
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1130698; hg19: chr11-838542;